Genetic Variant SERPINA6:p.Asp337Asp (chr14-94306092-G-A) – ACMG Classification: Benign (-14 pts)

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_StrongBP6BP7BA1

The NM_001756.4(SERPINA6):c.1011C>T(p.Asp337Asp) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.137 in 1,613,700 control chromosomes in the GnomAD database, including 17,663 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.18 ( 3233 hom., cov: 32)

Exomes 𝑓: 0.13 ( 14430 hom. )

Consequence

SERPINA6
NM_001756.4 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -2.21

Variant links:

Genes affected

SERPINA6 (HGNC:1540): (serpin family A member 6) This gene encodes an alpha-globulin protein with corticosteroid-binding properties. This is the major transport protein for glucorticoids and progestins in the blood of most vertebrates. The gene localizes to a chromosomal region containing several closely related serine protease inhibitors which may have evolved by duplication events. [provided by RefSeq, Jul 2008]

SERPINA6 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -14 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.84).

BP6

Variant 14-94306092-G-A is Benign according to our data. Variant chr14-94306092-G-A is described in ClinVar as [Benign]. Clinvar id is 3056658.Status of the report is no_assertion_criteria_provided, 0 stars.

BP7

Synonymous conserved (PhyloP=-2.21 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.324 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINA6	NM_001756.4 link	c.1011C>T	p.Asp337Asp	synonymous_variant	Exon 4 of 5	ENST00000341584.4	NP_001747.3	P08185A0A2Z4LCH4
SERPINA6	XM_047431827.1 link	c.1182C>T	p.Asp394Asp	synonymous_variant	Exon 4 of 5		XP_047287783.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
SERPINA6	ENST00000341584.4 link	c.1011C>T	p.Asp337Asp	synonymous_variant	Exon 4 of 5	1	NM_001756.4	ENSP00000342850.3	P08185
SERPINA6	ENST00000555056.1 link	n.*323C>T		non_coding_transcript_exon_variant	Exon 4 of 5	2		ENSP00000451045.1	G3V350
SERPINA6	ENST00000555056.1 link	n.*323C>T		3_prime_UTR_variant	Exon 4 of 5	2		ENSP00000451045.1	G3V350

Frequencies

GnomAD3 genomes

AF:

0.182

AC:

27633

AN:

152014

Hom.:

3220

Cov.:

show subpopulations

Gnomad AFR

AF:

0.329

Gnomad AMI

AF:

0.0844

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.199

Gnomad EAS

AF:

0.00501

Gnomad SAS

AF:

0.0890

Gnomad FIN

AF:

0.108

Gnomad MID

AF:

0.212

Gnomad NFE

AF:

0.136

Gnomad OTH

AF:

0.193

GnomAD3 exomes

AF:

0.130

AC:

32716

AN:

251364

Hom.:

2712

AF XY:

0.127

AC XY:

17215

AN XY:

135848

show subpopulations

Gnomad AFR exome

AF:

0.328

Gnomad AMR exome

AF:

0.0911

Gnomad ASJ exome

AF:

0.210

Gnomad EAS exome

AF:

0.00500

Gnomad SAS exome

AF:

0.0887

Gnomad FIN exome

AF:

0.108

Gnomad NFE exome

AF:

0.141

Gnomad OTH exome

AF:

0.150

GnomAD4 exome

AF:

0.133

AC:

194159

AN:

1461568

Hom.:

14430

Cov.:

AF XY:

0.131

AC XY:

95232

AN XY:

727120

show subpopulations

Gnomad4 AFR exome

AF:

0.334

Gnomad4 AMR exome

AF:

0.0975

Gnomad4 ASJ exome

AF:

0.207

Gnomad4 EAS exome

AF:

0.00562

Gnomad4 SAS exome

AF:

0.0902

Gnomad4 FIN exome

AF:

0.110

Gnomad4 NFE exome

AF:

0.134

Gnomad4 OTH exome

AF:

0.145

GnomAD4 genome

AF:

0.182

AC:

27678

AN:

152132

Hom.:

3233

Cov.:

AF XY:

0.177

AC XY:

13126

AN XY:

74366

show subpopulations

Gnomad4 AFR

AF:

0.329

Gnomad4 AMR

AF:

0.129

Gnomad4 ASJ

AF:

0.199

Gnomad4 EAS

AF:

0.00502

Gnomad4 SAS

AF:

0.0889

Gnomad4 FIN

AF:

0.108

Gnomad4 NFE

AF:

0.136

Gnomad4 OTH

AF:

0.191

Alfa

AF:

0.154

Hom.:

1754

Bravo

AF:

0.191

Asia WGS

AF:

0.0750

AC:

260

AN:

3478

EpiCase

AF:

0.150

EpiControl

AF:

0.143

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

SERPINA6-related disorder

Benign:1

Dec 07, 2023

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

2.9

DANN

Benign

0.20

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over